XIAP

What is XIAP Protein?

XIAP gene (X-linked inhibitor of apoptosis) is a protein coding gene which situated on the long arm of chromosome X at locus Xq25. This gene encodes a protein that belongs to a family of apoptotic suppressor proteins. Members of this family share a conserved motif termed, baculovirus IAP repeat, which is necessary for their anti-apoptotic function. This protein functions through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 and inhibits apoptosis induced by menadione, a potent inducer of free radicals, and interleukin 1-beta converting enzyme. This protein also inhibits at least two members of the caspase family of cell-death proteases, caspase-3 and caspase-7. The XIAP protein is consisted of 497 amino acids and XIAP molecular weight is approximately 56.7 kDa.

What is the Function of XIAP Protein?

XIAP is basically this protein that steps in to prevent cells from going into self-destruct mode, also known as apoptosis. It does its job by latching onto certain proteins like TRAF1 and TRAF2, which are involved in cell death signaling. XIAP is pretty effective at stopping apoptosis triggered by things like menadione, which produces a ton of free radicals, and another factor called interleukin 1-beta converting enzyme. Plus, it keeps caspase-3 and caspase-7, which are part of the cell's death machinery, in check, ensuring cells stay alive when they need to.

XIAP Related Signaling Pathway

The XIAP protein plays a crucial role in blocking cell death. It achieves this by inhibiting certain caspases, specifically caspase-3 and caspase-7, which are enzymes that drive the apoptosis or programmed cell death process. In simpler terms, XIAP acts as a bodyguard for cells, stopping them from self-destructing under stress conditions, like when exposed to harmful compounds such as free radicals. This protective mechanism is part of a broader signaling pathway where XIAP interacts with other proteins, like TRAF1 and TRAF2, to ensure cell survival and prevent unwanted cell death, especially in situations where cells might be under attack, thereby maintaining normal cellular functions and health.

Fig1. E3 ubiquitin-ligase substrates of XIAP. (S Galbán, 2009)

XIAP Related Diseases

XIAP, short for X-linked inhibitor of apoptosis protein, is a key player in the body's way of preventing cell death. It's like a molecular bodyguard, keeping certain cells from self-destructing when they're exposed to stress or damage signals that typically trigger apoptosis, or programmed cell death. Now, when XIAP goes haywire, it can be linked to various diseases. For example, if it's not working properly, it might fail to stop certain harmful processes that lead to excessive cell death, which is tied to neurodegenerative diseases like Parkinson's. On the flip side, if XIAP is overly active, it might prevent cancer cells from dying, contributing to the progression of cancers by letting damaged cells survive. Hence, XIAP's role in keeping the balance of cell death processes is crucial, and any imbalance can connect to several diseases, making it a target of interest for therapies aiming to either ramp up or dial down its activity.

Bioapplications of XIAP

XIAP, short for X-linked inhibitor of apoptosis protein, has some intriguing bioapplications. In simple terms, it's like a bodyguard for cells, stopping them from self-destructing by blocking certain proteins called caspases that lead to cell death. Because of this talent, scientists see potential in using XIAP to develop therapies for diseases where cell death is a problem, like certain neurodegenerative disorders and heart conditions. Plus, there's research into how tackling XIAP might help cancer treatments since it sometimes helps cancer cells dodge death. So, XIAP is pretty much a hot topic in the world of science and medicine!

Case Study 1: Si-Eun Yun, 2018

Regulating cell death, or apoptosis, is crucial for treating cancer and neurodegenerative diseases. Researchers have been exploring ways to either trigger or stop cell death to tackle these conditions. To develop effective drugs, it's important to understand how the target molecules work and their biochemical properties. XIAP is a standout among these molecules because it can block cell death by stopping certain enzymes, caspase-9 and -3/7, from doing their job. Although XIAP is a promising target for controlling cell death, studying its biochemical and biophysical aspects is no easy task. In one study, scientists used a system to prepare and analyze XIAP and its variants, 242Δ and Δ230, which act as blockers for caspase-9 and -3/7. These inhibitors were grown in E. coli bacteria and expressed at high concentrations. By applying a straightforward and quick purification method, researchers managed to achieve a high yield of these inhibitors at about 90% purity.

Fig1. Expression of the XIAP proteins.

Fig2. Immunological verification of CASP-3 inhibition by XIAP.

Case Study 2: Elena Coccia, 2020

The long version of the Fas apoptosis inhibitory molecule, known as FAIM-L, acts as a neuron-specific blocker against cell death receptors, helping manage neuron survival and flexibility. It combats cell death by teaming up with the X-linked inhibitor of apoptosis protein (XIAP), which stops the enzymes called caspases that drive apoptosis. Normally, XIAP levels are controlled by a system that tags it for breakdown, but when FAIM-L pairs with XIAP, it shields XIAP from being destroyed, allowing it to keep caspases in check. This combo also influences other roles caspases play, like how nerve cells adjust over time, such as during processes that weaken synaptic connections. The exact workings of FAIM-L are not fully clear since its binding sites aren't well-defined. Through certain testing, researchers uncovered that FAIM-L and SIVA-1, a protein inclined to promote cell death, can interact. SIVA-1 disrupts the FAIM-L and XIAP partnership, which leads to XIAP being tagged for breakdown, caspase activation, and neuron death. Additionally, SIVA-1 aids in the internalization of synaptic receptors, especially when there's chemical signaling to weaken synapses, by triggering non-death-related caspase actions.

Fig3. Immunoprecipitation of Myc-XIAP using anti-Myc antibody.

Fig4. The membrane was blotted with FAIM-L, XIAP, and HA to detect SIVA-1, and tubulin was used as a loading control.

XIAP has several biochemical functions, for example, cysteine-type endopeptidase inhibitor activity involved in apoptotic process,ligase activity,protein binding. Some of the functions are cooperated with other proteins, some of the functions could acted by XIAP itself. We selected most functions XIAP had, and list some proteins which have the same functions with XIAP. You can find most of the proteins on our site.

XIAP has direct interactions with proteins and molecules. Those interactions were detected by several methods such as yeast two hybrid, co-IP, pull-down and so on. We selected proteins and molecules interacted with XIAP here. Most of them are supplied by our site. Hope this information will be useful for your research of XIAP.

CASP9;HTRA2